The proposed project consists of a study of the physiology of synapses developing in vivo. The objective is to gain an understanding of the processes involved in the formation, maturation and long-term maintenance of synaptic contacts. Particular attention will be paid to the specific changes in physiology and morpholooy which occur during development. We will examine such features as spontaneous and evoked transmitter release, morphology of synaptic contacts, electrical characteristics of postsynaptic cell membrane, and transmitter sensitivity of postsynaptic membrane. An attempt will be made to determine the relative chronology of the observed changes, and how they influence one another. The initial development of synapses will be studied in three systems: newly developing muscles in the regenerating limb of the salamander,frogs undergoing metamorphosis, and rat embryos. Synapses appearing during reinnervation of mature tissue will be examined in salamander leg muscle and frog-heart parasympathetic ganglion cells. An investigation will also be made of developing salamander muscle and mature frog-heart ganglia maintained in tissue culture.